CA2456606A1 - 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity - Google Patents

4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity Download PDF

Info

Publication number
CA2456606A1
CA2456606A1 CA002456606A CA2456606A CA2456606A1 CA 2456606 A1 CA2456606 A1 CA 2456606A1 CA 002456606 A CA002456606 A CA 002456606A CA 2456606 A CA2456606 A CA 2456606A CA 2456606 A1 CA2456606 A1 CA 2456606A1
Authority
CA
Canada
Prior art keywords
group
disorders
alkyl
substituted
amino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002456606A
Other languages
French (fr)
Other versions
CA2456606C (en
Inventor
Cornelis G. Kruse
Josephus H.M. Lange
Jacobus Tipker
Arnoldus H.J. Herremans
Herman H. Van Stuivenberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Healthcare Products BV
Original Assignee
Solvay Pharmaceuticals B.V.
Cornelis G. Kruse
Josephus H.M. Lange
Jacobus Tipker
Arnoldus H.J. Herremans
Herman H. Van Stuivenberg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Solvay Pharmaceuticals B.V., Cornelis G. Kruse, Josephus H.M. Lange, Jacobus Tipker, Arnoldus H.J. Herremans, Herman H. Van Stuivenberg filed Critical Solvay Pharmaceuticals B.V.
Publication of CA2456606A1 publication Critical patent/CA2456606A1/en
Application granted granted Critical
Publication of CA2456606C publication Critical patent/CA2456606C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

The present invention relates to a group of novel 4,5-dihydro-1H-pyrazole derivatives which are potent cannabinoid (CB1) receptor antagonists with utility for the treatment of diseases connected with disorders of the cannabinoid system. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification. The invention also relates to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component.

Claims (5)

1. Compounds of the general formula (I) wherein - R and R1 independently represent phenyl, thienyl or pyridyl which groups may be substituted with 1, 2, 3 or 4 substituents Y, which can be the same or different, from the group C1-3-alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1_3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl, or R and/or R1, represent naphtyl, - R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy, - R3 represents a hydrogen atom or a branched or unbranched C1_8 alkyl group or a C3_7 cycloalkyl group which alkyl group or cycloalkyl group may be substituted with a hydroxy group, - R4 represents a C2-10 branched or unbranched heteroalkyl group, C3_6 non-aromatic heterocycloalkyl group or C4_10 non-aromatic heterocycloalkyl-alkyl group which groups contain one or more heteroatoms from the group (O, N, S) or a -SO2- group, which C2_10 branched or unbranched heteroalkyi group, C3_6 non-aromatic heterocycloalkyl group or C4_10 non-aromatic heterocycloalkyl-alkyl group may be substituted with a keto group, trifluoromethyl group, C1_3 alkyl group, hydroxy, amino, monoalkylamino, or dialkylamino group or a fluoro atom, or R4 represents an amino, hydroxy, phenoxy or benzyloxy group, or R4 represents a C1_8 alkoxy, C3_8 alkenyl, C5_8 cycloalkenyl or C6_9 cycloalkenylalkyl group which groups may contain a sulphur, nitrogen or oxygen atom, a keto group or -SO2- group, which alkoxy, alkenyl and cycloalkenyl groups may be substituted with a hydroxy group, a trifluoromethyl group, an amino group, a monoalkylamino group or dialkylamino group or a fluoro atom, or R4 represents a C2_5 alkyl group which alkyl group contains a fluoro atom, or R4 represents an imidazolylalkyl group, benzyl, pyridylmethyl, phenethyl or thienyl group, or represents a substituted phenyl, benzyl, pyridyl, thienyl, pyridylmethyl or phenethyl group wherein the aromatic rings are substituted with 1, 2 or 3 of the substituents Y, wherein Y has the meaning as indicated above, or when R3 is H or methyl, R4 may represent a group NR6R7wherein - R6 and R7 are the same or different and represent C2_4 alkyl , C2_4 trifluoroalkyl or R6 represents a methyl group with the proviso that R7 represents a C2_4 alkyl group, or R6 and R7 - together with the nitrogen atom to which they are bonded - form a saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms which heterocyclic moiety may contain an oxygen or sulphur atom or a keto group or -SOZ- group or an additional nitrogen atom, which saturated or unsaturated heterocyclic moiety may be substituted with a C1_4 alkyl group, or - R3 and R4 together with the nitrogen atom to which they are bonded from a saturated or unsaturated, monocyclic or bicyclic heterocyclic moiety having 4 to ring atoms, which heterocyclic moiety may contain one or more atoms from the group (O, N, S) or a keto group or -S02- group, which moiety may be substituted with a C1_4 alkyl, hydroxyalkyl, phenyl, thienyl, pyridyl, amino, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylamino, dialkylamino, aminoalkyl, azetidinyl, pyrrolidinyl, piperidinyl or hexahydro-1 H-azepinyl group, - R5 represents benzyl, phenyl, thienyl or pyridyl which may be substituted with 1, 2, 3 or 4 substituents Y, wherein Y has the meaning as indicated above, which can be the same or different, or R5 represents C1_8 branched or unbranched alkyl, C3_8 alkenyl, C3_10 cycloalkyl, C5_10 bicycloalkyl, C6_10 tricycloalkyl or C5_8 cycloalkenyl or R5 represents naphtyl.

and tautomers, prodrugs, stereoisomers and salts thereof.
2. Pharmaceutical compositions containing a pharmacologically active amount of at least one compound as claimed in claim 1 as an active component.
3. Method of preparing pharmaceutical compositions as claimed in claim 2 characterised in that a compound as claimed in claim 1 is brought in a form suitable for administration.
4. Use of a compound as claimed in claim 1 for the preparation of a pharmaceutical composition for the treatment of disorders involving cannabinoid neurotransmission.
5. Use as claimed in claim 4 characterised in that said disorders are psychiatric disorders such as psychosis, anxiety, depression, attention deficits, memory disorders, cognitive disorders, appetite disorders, obesity, addiction, appetence, drug dependence and neurological disorders such as neurodegenerative disorders, dementia, dystonia, muscle spasticity, tremor, epilepsy, multiple sclerosis, traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, epilepsy, Huntington's disease, Tourette's syndrome, cerebral ischaemia, cerebral apoplexy, craniocerebral trauma, stroke, spinal cord injury, neuroinflammatory disorders, plaque sclerosis, viral encephalitis, demyelinisation related disorders, as well as for the treatment of pain disorders, including neuropathic pain disorders, and other diseases involving cannabinoid neurotransmission, including the treatment of septic shock, glaucoma, cancer, diabetes, emesis, nausea, asthma, respiratory diseases, gastrointestinal disorders, gastric ulcers, diarrhoea and cardiovascular disorders.
CA2456606A 2001-09-21 2002-09-17 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity Expired - Fee Related CA2456606C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP01203850.1 2001-09-21
EP01203850 2001-09-21
PCT/EP2002/010433 WO2003026647A1 (en) 2001-09-21 2002-09-17 Novel 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity

Publications (2)

Publication Number Publication Date
CA2456606A1 true CA2456606A1 (en) 2003-04-03
CA2456606C CA2456606C (en) 2010-01-26

Family

ID=8181043

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2456606A Expired - Fee Related CA2456606C (en) 2001-09-21 2002-09-17 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity

Country Status (25)

Country Link
US (1) US7528162B2 (en)
EP (1) EP1429761B1 (en)
JP (1) JP4313671B2 (en)
KR (1) KR100903760B1 (en)
CN (2) CN101659639A (en)
AR (1) AR036596A1 (en)
AT (1) ATE344663T1 (en)
AU (1) AU2002333852B2 (en)
BR (1) BR0212044A (en)
CA (1) CA2456606C (en)
DE (1) DE60215960T2 (en)
DK (1) DK1429761T3 (en)
ES (1) ES2272809T3 (en)
HR (1) HRP20040085A2 (en)
HU (1) HUP0401567A3 (en)
IL (2) IL160081A0 (en)
MX (1) MXPA04002583A (en)
NO (1) NO20041176L (en)
PL (1) PL368441A1 (en)
PT (1) PT1429761E (en)
RU (1) RU2299199C2 (en)
SI (1) SI1429761T1 (en)
UA (1) UA78523C2 (en)
WO (1) WO2003026647A1 (en)
ZA (1) ZA200402099B (en)

Families Citing this family (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2456606C (en) 2001-09-21 2010-01-26 Solvay Pharmaceuticals B.V. 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity
CA2478183C (en) 2002-03-12 2010-02-16 Merck & Co. Inc. Substituted amides
US7129239B2 (en) 2002-10-28 2006-10-31 Pfizer Inc. Purine compounds and uses thereof
US7247628B2 (en) 2002-12-12 2007-07-24 Pfizer, Inc. Cannabinoid receptor ligands and uses thereof
US7772188B2 (en) 2003-01-28 2010-08-10 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of gastrointestinal disorders
US7329658B2 (en) 2003-02-06 2008-02-12 Pfizer Inc Cannabinoid receptor ligands and uses thereof
US7176210B2 (en) 2003-02-10 2007-02-13 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7145012B2 (en) 2003-04-23 2006-12-05 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7141669B2 (en) 2003-04-23 2006-11-28 Pfizer Inc. Cannabiniod receptor ligands and uses thereof
US7268133B2 (en) 2003-04-23 2007-09-11 Pfizer, Inc. Patent Department Cannabinoid receptor ligands and uses thereof
US7232823B2 (en) 2003-06-09 2007-06-19 Pfizer, Inc. Cannabinoid receptor ligands and uses thereof
AR045533A1 (en) * 2003-09-02 2005-11-02 Solvay Pharm Gmbh USE OF AN ANTAGONIST CB1 RECEIVER COMPOUND, PHARMACEUTICAL COMPOSITION AND TREATMENT METHOD AND / OR PROPHYLAXIS OF DISEASES RELATED TO SUCH CB1 RECEIVER
US20050239859A2 (en) * 2003-09-03 2005-10-27 Solvay Pharmaceuticals Gmbh Novel medical uses of 4,5-dihydro-1h-pyrazole derivatives having cb1- antagonistic activity
FR2861301B1 (en) * 2003-10-24 2008-07-11 Sanofi Synthelabo USE OF THE PYRAZOLE DERIVATIVE FOR THE PREPARATION OF MEDICAMENTS USEFUL IN THE PREVENTION AND TREATMENT OF METABOLIC SYNDROME.
MXPA06004434A (en) * 2003-10-24 2006-06-20 Solvay Pharm Gmbh Novel medical uses of compounds showing cb1.
AR046132A1 (en) * 2003-10-24 2005-11-23 Solvay Pharm Gmbh PHARMACEUTICAL COMPOSITION CONTAINING AT LEAST ONE COMPOUND WITH RECEIVER ACTIVITY OF CB1, OR A PROFARMACO, TAUTOMERO OR SALT OF THE SAME, AS A SUITABLE ACTIVE COMPONENT FOR THE TREATMENT AND / OR PROFILAXIS OF DISEASES RELATED TO THE RECEIVER CB1 IN PATIENTS OR YOUTH PATIENTS THE TREATMENT
FR2861302A1 (en) * 2003-10-24 2005-04-29 Sanofi Synthelabo Use of pyrazole derivative as cannabinoid CB1 receptor antagonist, for treatment and prevention of metabolic syndrome, particularly cardiovascular risks and dyslipidemia associated with obesity
FR2861300B1 (en) * 2003-10-24 2008-07-11 Sanofi Synthelabo USE OF A PYRAZOLE DERIVATIVE FOR THE PREPARATION OF MEDICAMENTS USEFUL IN THE PREVENTION AND TREATMENT OF METABOLIC SYNDROME
FR2861303A1 (en) * 2003-10-24 2005-04-29 Sanofi Synthelabo Use of pyrazole derivative as cannabinoid CB1 receptor antagonist, for treatment and prevention of metabolic syndrome, particularly cardiovascular risks, dyslipidemia and liver disease associated with obesity
US20050143441A1 (en) * 2003-10-27 2005-06-30 Jochen Antel Novel medical combination treatment of obesity involving 4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity
US20050124660A1 (en) * 2003-10-27 2005-06-09 Jochen Antel Novel medical uses of compounds showing CB1-antagonistic activity and combination treatment involving said compounds
CN100563651C (en) * 2004-01-30 2009-12-02 索尔瓦药物有限公司 1,3, 5-trisubstituted 4, 5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity
US7745476B2 (en) 2004-01-30 2010-06-29 Solvay Pharmaceuticals B.V. 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity
TW200533657A (en) 2004-02-17 2005-10-16 Esteve Labor Dr Substituted pyrazoline compounds, their preparation and use as medicaments
US7173044B2 (en) 2004-02-19 2007-02-06 Solvay Pharmaceuticals B.V. Imidazoline derivatives having CB1-antagonistic activity
PT1725536E (en) * 2004-02-19 2009-01-22 Solvay Pharm Bv Imidazoline derivatives having cb1-antagonistic activity
TWI335321B (en) * 2004-02-19 2011-01-01 Solvay Pharm Bv Imidazoline derivatives having cb1-antagonistic activity
WO2005097127A2 (en) 2004-04-02 2005-10-20 Merck & Co., Inc. Method of treating men with metabolic and anthropometric disorders
TW200602314A (en) 2004-05-28 2006-01-16 Tanabe Seiyaku Co A novel pyrrolidine compound and a process for preparing the same
US8030345B2 (en) 2004-07-12 2011-10-04 Cadila Healthcare Limited Tricyclic pyrazole derivatives as cannabinoid receptor modulators
US20060025448A1 (en) 2004-07-22 2006-02-02 Cadila Healthcare Limited Hair growth stimulators
KR100641875B1 (en) * 2004-09-15 2006-11-08 장창호 Liquid ink composition for marking pens and a method of manufacturing the same
RU2007119315A (en) 2004-10-25 2008-11-27 Зольвай Фармасьютиклз Гмбх (De) PHARMACEUTICAL COMPOSITIONS CONTAINING CB1 CANNABINOID RECEPTOR ANTAGONISTS AND POTASSIUM CHANNEL OPENERS INTENDED FOR TREATMENT OF TYPE I SUITERS, CREAM
JP2008545739A (en) 2005-06-02 2008-12-18 グレンマーク・ファーマシューティカルズ・エスエー Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and methods for their preparation
US7923465B2 (en) 2005-06-02 2011-04-12 Glenmark Pharmaceuticals S.A. Cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation
AU2006264649A1 (en) 2005-06-30 2007-01-11 Prosidion Limited GPCR agonists
EP1743890A1 (en) * 2005-07-15 2007-01-17 Laboratorios Del Dr. Esteve, S.A. 4,5-Dihydro-1H-pyrazole derivatives, their preparation and use as medicaments
EP1749820A1 (en) * 2005-07-15 2007-02-07 Laboratorios Del Dr. Esteve, S.A. Salts of substituted pyrazoline compounds, their preparation and use as medicaments
EP1743892A1 (en) * 2005-07-15 2007-01-17 Laboratorios del Dr. Esteve S.A. Substituted pyrazoline compounds, their preparation and use as medicaments
WO2007009705A1 (en) * 2005-07-15 2007-01-25 Laboratorios Del Dr. Esteve, S.A. (rac)-n-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydr0-1h-pyrazole-3-carboxamide hydrates
EP1749821A1 (en) * 2005-07-15 2007-02-07 Laboratorios Del Dr. Esteve, S.A. Quaternary ammonium salts of substituted pyrazoline compounds, their preparation and use as medicaments
EP1749819A1 (en) * 2005-07-15 2007-02-07 Laboratorios Del Dr. Esteve, S.A. (rac)-N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide hydrates
ES2326460B1 (en) * 2005-07-15 2010-04-19 Laboratorios Del Dr. Esteve, S.A. QUATERNARY AMMONIUM SALTS OF SUBSTITUTED PIRAZOLINE COMPOUNDS, THEIR PREPARATION AND USE AS MEDICINES.
ES2330992B1 (en) * 2005-07-15 2010-07-06 Laboratorios Del Dr. Esteve, S.A. HETEROCICLILS REPLACED PIRAZOLINE COMPOUNDS, ITS PREPARATION AND USE AS MEDICATIONS.
BRPI0616995A2 (en) * 2005-08-17 2011-07-05 Solvay Pharm Gmbh pharmaceutical composition, and use of kv1.3 potassium channel inhibitor in drug preparation
ES2389569T3 (en) * 2006-05-05 2012-10-29 Jenrin Discovery Inverse antagonists / agonists of cannabinoid receptors
US7964728B2 (en) 2006-07-06 2011-06-21 Solvay Pharmaceuticals B.V. Azaindole derivatives with a combination of partial nicotinic acetyl-choline receptor agonism and dopamine reuptake inhibition
RU2009108280A (en) 2006-08-08 2010-09-20 Санофи-Авентис (Fr) Arylamino-arylalkyl-substituted imidazolidine-2,4-dione, methods for their preparation containing these compounds and their use
AR062907A1 (en) * 2006-09-22 2008-12-17 Solvay Pharm Bv DERIVATIVES OF SULFONILPIRAZOL AND SULFONILPIRAZOLINCARBOXAMIDINE AS ANTAGONISTS OF 5-HT6
WO2008046905A1 (en) * 2006-10-20 2008-04-24 Solvay Pharmaceuticals B.V. Micellar nanoparticles of chemical substances
US7923026B2 (en) 2006-10-20 2011-04-12 Solvay Pharmaceuticals B.V. Embedded micellar nanoparticles
GB0700122D0 (en) 2007-01-04 2007-02-14 Prosidion Ltd GPCR agonists
AR064735A1 (en) 2007-01-04 2009-04-22 Prosidion Ltd GPCR AGONISTS AND PHARMACEUTICAL COMPOSITION BASED ON THE COMPOUND
JP2010514828A (en) 2007-01-04 2010-05-06 プロシディオン・リミテッド Piperidine GPCR agonist
AR064736A1 (en) 2007-01-04 2009-04-22 Prosidion Ltd GPCR AGONISTS
EP2114936A1 (en) 2007-01-04 2009-11-11 Prosidion Limited Piperidine gpcr agonists
CA2688161C (en) 2007-06-04 2020-10-20 Kunwar Shailubhai Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
US8410135B2 (en) 2007-06-15 2013-04-02 Solvay Pharmaceuticals B.V. 4,5 dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators
AU2008263915A1 (en) * 2007-06-15 2008-12-18 Solvay Pharmaceuticals B.V. 4,5-dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators
EP2025674A1 (en) 2007-08-15 2009-02-18 sanofi-aventis Substituted tetra hydro naphthalines, method for their manufacture and their use as drugs
GB0720389D0 (en) 2007-10-18 2008-11-12 Prosidion Ltd G-Protein Coupled Receptor Agonists
GB0720390D0 (en) 2007-10-18 2007-11-28 Prosidion Ltd G-Protein coupled receptor agonists
US7655685B2 (en) * 2007-11-02 2010-02-02 Jenrin Discovery, Inc. Cannabinoid receptor antagonists/inverse agonists useful for treating metabolic disorders, including obesity and diabetes
ES2716407T3 (en) 2007-11-30 2019-06-12 Zynerba Pharmaceuticals Inc Prodrugs of tetrahydrocannabinol, compositions comprising prodrugs of tetrahydrocannabinol and methods for their use
ES2522968T3 (en) 2008-06-04 2014-11-19 Synergy Pharmaceuticals Inc. Guanylate cyclase agonists useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
WO2010003624A2 (en) 2008-07-09 2010-01-14 Sanofi-Aventis Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof
ES2624828T3 (en) 2008-07-16 2017-07-17 Synergy Pharmaceuticals Inc. Guanylate cyclase agonists useful for the treatment of gastrointestinal disorders, inflammation, cancer and others
EP2151234A1 (en) * 2008-07-28 2010-02-10 Laboratorios Del. Dr. Esteve, S.A. Pharmaceutical formulation comprising a CB1-receptor compound in a solid solution and/or solid dispersion
WO2010047982A1 (en) 2008-10-22 2010-04-29 Merck Sharp & Dohme Corp. Novel cyclic benzimidazole derivatives useful anti-diabetic agents
CA2741672A1 (en) 2008-10-31 2010-05-06 Merck Sharp & Dohme Corp. Novel cyclic benzimidazole derivatives useful anti-diabetic agents
WO2010079241A1 (en) 2009-01-12 2010-07-15 Fundacion Hospital Nacional De Paraplejicos Para La Investigacion Y La Integracion Use of antagonists and/or inverse agonists of cb1 receptors for the preparation of drugs that increase motor neuron excitability
US8217038B2 (en) 2009-10-07 2012-07-10 Jenrin Discovery, Inc. Cannabinoid receptor antagonists/inverse agonists useful for treating metabolic disorders, including obesity and diabetes
WO2011106273A1 (en) 2010-02-25 2011-09-01 Merck Sharp & Dohme Corp. Novel cyclic benzimidazole derivatives useful anti-diabetic agents
EP2582709B1 (en) 2010-06-18 2018-01-24 Sanofi Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
DE102010044131A1 (en) 2010-11-18 2012-05-24 Bayer Schering Pharma Aktiengesellschaft Substituted sodium 1H-pyrazole-5-olate
US8580768B2 (en) 2010-11-18 2013-11-12 Jenrin Discovery, Inc. Cannabinoid receptor antagonists-inverse agonists useful for treating metabolic disorders, including obesity and diabetes
EA025380B1 (en) 2011-02-25 2016-12-30 Мерк Шарп Энд Домэ Корп. Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents
EP2683699B1 (en) 2011-03-08 2015-06-24 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
US8895547B2 (en) 2011-03-08 2014-11-25 Sanofi Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof
EP2683701B1 (en) 2011-03-08 2014-12-24 Sanofi Oxathiazine derivatives substituted with benzyl or heteromethylene groups, method for their preparation, their usage as medicament, medicament containing same and its use
EP2683704B1 (en) 2011-03-08 2014-12-17 Sanofi Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120051A1 (en) 2011-03-08 2012-09-13 Sanofi Benzyl-oxathiazine derivates substituted with adamantane or noradamantane, medicaments containing said compounds and use thereof
US8871758B2 (en) 2011-03-08 2014-10-28 Sanofi Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof
EP2683702B1 (en) 2011-03-08 2014-12-24 Sanofi New substituted phenyl oxathiazine derivatives, method for their manufacture, medicines containing these compounds and their application
WO2012120054A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
US8901114B2 (en) 2011-03-08 2014-12-02 Sanofi Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof
US8680131B2 (en) 2012-07-25 2014-03-25 Jenrin Discovery, Inc. Cannabinoid receptor antagonists/inverse agonists useful for treating disease conditions, including metabolic disorders and cancers
KR20150036245A (en) 2012-08-02 2015-04-07 머크 샤프 앤드 돔 코포레이션 Antidiabetic tricyclic compounds
US11155521B2 (en) 2012-11-13 2021-10-26 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Cannabinoid receptor mediating compounds
EP2919779B1 (en) 2012-11-13 2021-01-06 The U.S.A. as represented by the Secretary, Department of Health and Human Services Cannabinoid receptor mediating compounds
RU2015140066A (en) 2013-02-22 2017-03-30 Мерк Шарп И Доум Корп. ANTI-DIABETIC BICYCLIC COMPOUNDS
WO2014139388A1 (en) 2013-03-14 2014-09-18 Merck Sharp & Dohme Corp. Novel indole derivatives useful as anti-diabetic agents
US9486494B2 (en) 2013-03-15 2016-11-08 Synergy Pharmaceuticals, Inc. Compositions useful for the treatment of gastrointestinal disorders
EP2970384A1 (en) 2013-03-15 2016-01-20 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
JP6606491B2 (en) 2013-06-05 2019-11-13 シナジー ファーマシューティカルズ インコーポレイテッド Ultra high purity agonist of guanylate cyclase C, method for producing and using the same
WO2015051496A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
US10329259B2 (en) 2014-05-09 2019-06-25 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Pyrazole derivatives and their use as cannabinoid receptor mediators
EP3423448A1 (en) * 2016-03-04 2019-01-09 The U.S.A. as represented by the Secretary, Department of Health and Human Services Cannabinoid receptor mediating compounds
US11072602B2 (en) 2016-12-06 2021-07-27 Merck Sharp & Dohme Corp. Antidiabetic heterocyclic compounds

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL158178B (en) * 1974-07-12 1978-10-16 Philips Nv METHOD OF PREPARING INSECTICIDE PREPARATIONS CONTAINING A PYRAZOLINE DERIVATIVE, SO PREPARED PREPARATIONS, AND METHOD OF PREPARING PYRAZOLINE DERIVATIVES WITH INSECTICIDE ACTION.
FR2692575B1 (en) * 1992-06-23 1995-06-30 Sanofi Elf NOVEL PYRAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
US5292736A (en) * 1993-02-26 1994-03-08 Sterling Winthrop Inc. Morpholinoalkylindenes as antiglaucoma agents
US6117889A (en) * 1994-04-01 2000-09-12 University Of Virginia 7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents
US5616601A (en) * 1994-07-28 1997-04-01 Gd Searle & Co 1,2-aryl and heteroaryl substituted imidazolyl compounds for the treatment of inflammation
US6103708A (en) * 1998-05-12 2000-08-15 American Home Products Corporation Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
FR2789079B3 (en) * 1999-02-01 2001-03-02 Sanofi Synthelabo PYRAZOLECARBOXYLIC ACID DERIVATIVE, ITS PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
CO5170501A1 (en) 1999-04-14 2002-06-27 Novartis Ag USEFUL REPLACED BLUES FOR THE TREATMENT OF DISEASES MEDIATED BY TNFa eIL-1 AND DISEASES OF THE OSEO METABOLISM
CN1205188C (en) 2000-03-23 2005-06-08 索尔瓦药物有限公司 4,5-dihydro-1h-pyrazole derivatives having cbi-antagonistic activity
CA2456606C (en) 2001-09-21 2010-01-26 Solvay Pharmaceuticals B.V. 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity

Also Published As

Publication number Publication date
BR0212044A (en) 2004-08-17
JP4313671B2 (en) 2009-08-12
KR20040035823A (en) 2004-04-29
HUP0401567A3 (en) 2005-06-28
DE60215960T2 (en) 2007-03-01
MXPA04002583A (en) 2004-06-18
EP1429761B1 (en) 2006-11-08
IL160081A0 (en) 2004-06-20
SI1429761T1 (en) 2007-02-28
ES2272809T3 (en) 2007-05-01
JP2005503427A (en) 2005-02-03
AU2002333852B2 (en) 2006-07-13
HUP0401567A2 (en) 2005-01-28
RU2004107131A (en) 2005-08-20
NO20041176L (en) 2004-06-21
EP1429761A1 (en) 2004-06-23
CN1555262A (en) 2004-12-15
IL160081A (en) 2009-08-03
PT1429761E (en) 2007-02-28
US20040248944A1 (en) 2004-12-09
ATE344663T1 (en) 2006-11-15
DE60215960D1 (en) 2006-12-21
DK1429761T3 (en) 2007-02-05
WO2003026647A1 (en) 2003-04-03
UA78523C2 (en) 2007-04-10
US7528162B2 (en) 2009-05-05
HRP20040085A2 (en) 2004-08-31
RU2299199C2 (en) 2007-05-20
KR100903760B1 (en) 2009-06-19
PL368441A1 (en) 2005-03-21
CN101659639A (en) 2010-03-03
AR036596A1 (en) 2004-09-22
ZA200402099B (en) 2005-04-26
CA2456606C (en) 2010-01-26

Similar Documents

Publication Publication Date Title
CA2456606A1 (en) 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity
CA2442245A1 (en) 4,5-dihydro-1h-pyrazole derivatives having potent cb1-antagonistic activity
CA2462692A1 (en) Thiazole derivatives having cb1-antagonistic, agonistic or partial agonistic activity
CA2491394A1 (en) 1h-1,2,4-triazole-3-carboxamide derivatives as cannabinoid-cb1 receptor ligands
CA2457444A1 (en) 1h-imidazole derivatives having cb1 agonistic, cb1 partial agonistic or cb1- antagonistic activity
RU2006131132A (en) 1,3,5, -TRISubstituted derivatives of 4,5-dihydro-1H-pyrazole possessing CB1-antagonistic activity
CA2401832A1 (en) 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity
HUP0303148A2 (en) 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity, pharmaceutical compositions containing the compounds and processes for their preparation
RU2006133373A (en) IMIDAZOLINE DERIVATIVES WITH CB1-ANTAGONISTIC ACTIVITY
CA2482004A1 (en) Compounds having unique cb1 receptor binding selectivity and methods for their production and use
EP3409658B1 (en) Tetrahydronaphthalene derivative
ZA200606122B (en) 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazole derivatives having CB,-Antagonistic activity
FR2865205A1 (en) New O-aminocarbonylmethyl carbamate derivatives, useful for treating e.g. pain, cancer or neurodegeneration, are inhibitors of fatty acid amidohydrolase
CA2526991A1 (en) Piperidinium and pyrrolidinium derivatives as ligands for the muscarinic m3 receptor
IL173436A0 (en) 1h-imidazole derivatives as cannabinoid receptor modulators
RU2006117627A (en) NEW APPLICATIONS IN MEDICINE OF COMPOUNDS WITH ANTAGONISTIC ACTIVITY RELATING TO CB1, AND COMBINED TREATMENT USING THESE COMPOUNDS
JP2007513872A5 (en)
EP1756066B1 (en) Tetrasubstituted imidazole derivatives as cannabinoid cb1 receptor modulators with a high cb1/cb2 receptor subtype selectivity
US5331010A (en) 1-phenylalkanecarboxylic acid derivatives as anticonvulsant and neuroprotective agents
EP2158184A2 (en) 4,5-dihydro-(1h)-pyrazole derivatives as cannabinoid cb1 receptor modulators
MXPA06009508A (en) Imidazoline derivatives having cb1

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed